ABAT - 4-Aminobutyrate Aminotransferase | Elisa - Clia - Antibody - Protein

Background

ABAT (4-Aminobutyrate Aminotransferase), also known as GABA transaminase (GABA-T), is an enzyme that plays a critical role in the metabolism of gamma-aminobutyric acid (GABA), a key neurotransmitter in the central nervous system. This enzyme is involved in the catabolic pathway of GABA, converting it into succinic semialdehyde, which is then further metabolized into succinate, an intermediate of the tricarboxylic acid (TCA) cycle. ABAT is composed of two enzyme monomers, with each subunit having a molecular weight of 50 kDa. It has been identified that nearly a third of human synapses contain gamma-aminobutyric acid (GABA). GABA helps to slow down brain cell activity, acting as an inhibitory neurotransmitter when necessary to prevent the brain from being overwhelmed by excessive signals. Hence, GABA is commonly referred to as an inhibitory neurotransmitter.

Structural Features

ABAT is a pyridoxal phosphate (PLP)-dependent enzyme, which means it requires PLP (a form of vitamin B6) as a cofactor for its enzymatic activity. The key structural features include:

• Active Site: Contains the PLP cofactor bound to a lysine residue, essential for the transamination reaction.
• Dimeric Structure: ABAT functions as a homodimer, with each subunit contributing to the active site and overall stability of the enzyme.
• Binding Sites: Specific regions for substrate (GABA) and cofactor (PLP) binding.

Subtypes and Classification

ABAT is a member of the aminotransferase family of enzymes and does not have widely recognized subtypes. It is classified based on its function and the type of reaction it catalyzes:

• Aminotransferase: Enzyme that catalyzes the transfer of an amino group from an amino acid to a keto acid.
• GABA Metabolism: Specifically involved in the degradation of the neurotransmitter GABA.

Ligands and Interactions

The primary ligands and interactions for ABAT include:

• GABA (Gamma-Aminobutyric Acid): The main substrate for ABAT, which is deaminated to succinic semialdehyde.
• Pyridoxal Phosphate (PLP): The cofactor necessary for the transamination reaction.
• Succinic Semialdehyde: The product of the reaction, which is further metabolized in the TCA cycle.

Physiological Functions

ABAT has several important physiological roles:

• GABA Catabolism: By converting GABA into succinic semialdehyde, ABAT helps regulate GABA levels in the brain, maintaining the balance between excitatory and inhibitory signals.
• Energy Metabolism: The product succinic semialdehyde is converted into succinate, which enters the TCA cycle, linking neurotransmitter metabolism with cellular energy production.
• Neurotransmitter Regulation: Helps modulate synaptic levels of GABA, influencing neuronal excitability and function.

Clinical Implications

Deficiencies or dysfunctions in ABAT can lead to various clinical conditions:

• GABA-Transaminase Deficiency: A rare genetic disorder characterized by elevated GABA levels, leading to neurological symptoms such as seizures, developmental delays, and hypotonia.
• Neurological Disorders: Altered ABAT activity has been implicated in conditions such as epilepsy, schizophrenia, and mood disorders, due to its role in GABA metabolism.
• Metabolic Disorders: Given its role in the TCA cycle, ABAT dysfunction can also impact broader metabolic pathways.